Use Of Postmastectomy Radiation Therapy Research Articles

Benefit of scar boost radiation following postmastectomy radiation in female breast cancer: a retrospective analysis

Background: The use of postmastectomy radiation (PMRT) as a standard of care for female breast cancer is well established, with scar boost radiation being a discretionary choice. However, the efficacy of scar boost radiation remains a subject of debate. Methods: A retrospective analysis was conducted from medical records of female patients diagnosed with breast cancer who have undergone PMRT from January 2012 to January 2015 at Srinagarind Hospital, Khon Kaen University. The primary endpoint was chest wall local control (LC), and the secondary endpoints were risk factors associated with chest wall local recurrence (LR), locoregional recurrence (LRR) and overall survival (OS). Results: A total of 549 female patient records were included. The median follow-up time was 21 months. 31.51% of patients received scar boost radiation. The majority of the patients had ductal carcinoma (98.5%) and were histologically graded as grade 2 (44.6%) or 3 (39.0%). The estimated 10-yr chest wall local control rate was 82.14% (95% CI 68.12 - 99.04%) in scar boost group versus 93.18% (95% CI 89.58 - 96.92%) in no scar boost groups. No significant differences between the two groups were found in LR (HR 0.87, 95% CI 0.35-2.19), LRR (HR 1.20, 95% CI 0.60-2.37), and OS (HR 1.05, 95% CI 0.09-11.54). Subset analysis showed that lobular carcinoma was associated with LR and LRR (HR 11.32, 95% CI 3.24-39.54 and HR 5.65, 95% CI 1.71-18.61) while positive supraclavicular node was associated with LRR (HR 4.51, 95% CI 1.37-14.79). Scar boost radiation also resulted in a higher frequency of skin toxicity (grade 1-3), skin fibrosis (grade 1), and radiation pneumonitis (grade 1). Conclusions: There is no evidence supporting that scar boost radiation following PMRT in female breast cancer patients is superior in chest wall LC. Scar boost radiation is also statistically significantly associated with increased toxicity.

The trade-off of post-mastectomy radiotherapy usage for the breast cancer patients aged 70 years or older: a study based on SEER database

BackgroundThis study aimed to investigate the role of post-mastectomy radiotherapy (PMRT) in the female aged 70 years or older diagnosed with breast cancer, which is still controversial.MethodsThis retrospective study enrolled female breast cancer women aged 70 + years following mastectomy from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to reduce covariable imbalance. A nomogram was created to predict the 1,3,5-years overall survival (OS) and divide patients into three risk groups.ResultsAfter matching, PMRT were associated with significant improvement in breast cancer-specific survival (BCSS) and OS (p < 0.001). By contrast, the BCSS and OS benefit from PMRT were not significant in patients with T1N1 tumor (BCSS: HR = 0.716, p = 0.249;OS:HR = 0.908, p = 0.572), and T2N1 tumor (BCSS:HR = 0.866, p = 0.289;OS:HR = 0.879, p = 0.166). Stratified by subtype, the HR+/HER-2- subtype and the HR-/HER-2- subtype (all p < 0.001) have a significant prolonged survival, yet not significant BCSS difference are shown in the HER-2 + tumor. In the low-risk group as determined by the nomogram, the use of PMRT did not significantly improve OS (p = 0.203).ConclusionsThis study demonstrated that PMRT improves the survival of females with elderly breast cancer, while for T1-2N1 breast cancer patients, the omission of PMRT could be considered. Furthermore, the nomogram we constructed could be used as a decision tool for the omission of PMRT in low-risk elderly patients.

Post Mastectomy Radiation Therapy Impact on Clinical Outcomes of Male Breast Cancer: A Meta-Analysis of Comparative Studies

Male breast cancer accounts for less than 1 percent of all cancer diagnoses in men. Because it is rare, it does not lend itself to large, randomized trials. In general, the approach to the treatment of early, non-metastatic male breast cancer has largely been extrapolated from female breast cancer trials though it is deemed to be a different disease. Data on early-stage post mastectomy radiation therapy (PMRT) is limited, and its benefits remain unclear. We conducted this meta-analysis to determine the impact of PMRT on recurrence patterns and survival outcomes using the available male breast cancer data. A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of invasive non-metastatic male breast cancer (MBC), comparative studies of PMRT versus none, and studies that reported the incidence of local and distant recurrences as well as survival data in the compared arms. A meta-analysis using the Mantel-Haenszel method for calculating the weighted pooled relative risk (RR) under the fixed effects model was conducted. Subsequently, the heterogeneity statistic was incorporated to calculate the summary RR under the random effects model. Ten retrospective comparative studies with 3912 patients were included and analyzed. Eight studies reported survival data. Six and three studies reported local and distant recurrence incidence, respectively. PMRT did not have an impact on overall survival or distant recurrences. However, PMRT significantly lowered the RR of locoregional recurrences (RR = 0.53, 95% CI 0.31-0.92). In addition, when survival was analyzed by TNM stage and N status, PMRT was found to have a significant reduction in RR of death in stage III (RR = 0.85, 95% CI 0.75-0.97), N1 (RR = 0.77, 95% CI 0.61-0.98), and N2 (RR = 0.61, 95% CI 0.49-0.78) disease. This is the first meta-analysis to show that PMRT is associated with a lower relative risk of death in stage III MBC as well as N1 and N2 disease. It also demonstrates a significant reduction in RR of locoregional recurrences. In the absence of randomized clinical trials, it represents the most compelling data supporting the use of PMRT in this MBC patient population using MBC data.

A Population-Based Assessment of Long-Term Sexual Well-Being and Patient Satisfaction after Breast Reconstruction and Post-Mastectomy Radiation

In 2016, more than 40% of women who underwent mastectomy for breast cancer went on to have breast reconstruction, but there is little data regarding long-term cosmetic outcomes past 5 years after post-mastectomy radiation (PMRT) and reconstruction. This study aims to evaluate the difference in patient breast satisfaction and sexual well-being over time by receipt of reconstruction and PMRT. The iCanCare study is a population-based, longitudinal study of women diagnosed with breast cancer in 2014-15 identified in the Los Angeles and Georgia SEER registries. Women were surveyed during initial treatment and again approximately 6 years later in survivorship (2021-2022). Participants were asked about their "Sexual well-being after mastectomy" and "Satisfaction with breasts" using the Breast-Q, which was dichotomized into "high" and "low" scores (using the median), with a high score indicating increased satisfaction. We then evaluated whether satisfaction differed by treatment characteristics, using unadjusted odds ratios (OR) for categorical variables, calculated using the Chi-square test, or the Kruskal-Wallis test for continuous variables. Adjusted odds ratios were found using multivariable logistic regression models adjusting for treatment characteristics, diagnosis, age, BMI, education, and breast cancer stage. In this preliminary sample of 1191 respondents, 445 underwent mastectomy, of which 272 (61.12%) had reconstruction, and 65 (14.61%) had PMRT. Having breast reconstruction was associated with higher long-term sexual well-being (median score 36.30 vs. 22.20, OR 1.69, 95% confidence interval [CI] 1.09 - 2.64) and breast satisfaction scores (OR 1.53, 95% CI 1.01 - 2.33) compared to not having reconstruction. However, this improvement in sexual well-being was attenuated in women who additionally had PMRT (OR 0.83, CI 0.271 - 2.51). In women who did not have reconstruction after mastectomy, there was no statistically significant difference in sexual well-being scores regardless of the use of PMRT (OR 0.68, CI 0.39 - 1.22). Among respondents in adjusted models who did not receive PMRT, those with reconstruction had higher sexual well-being scores than those with without reconstruction (aOR 2.47, CI 1.34 - 4.56), though there was no statistically significant difference in breast satisfaction scores (p = 0.16) among the groups. Sexual well-being and breast satisfaction are improved with reconstruction 6 years after mastectomy for breast cancer. However, these improvements were attenuated for women who received PMRT. To our knowledge, this is the first study to look at long term outcomes of sexual well-being and treatment satisfaction after breast reconstruction for patients who underwent mastectomy for breast cancer. These data suggest that continued work should be done to optimize patient outcomes when combining PMRT and breast reconstruction.

Variation in Rates of Post-Mastectomy Radiotherapy Among Women with Early Invasive Breast Cancer in England and Wales: A Population-Based Cohort Study

AimsThis study examined whether patterns of post-mastectomy radiotherapy (PMRT) among women with early invasive breast cancer (EIBC) varied within England and Wales and explored the role of different patient factors in explaining any variation. Materials and methodsThe study used national cancer data on women aged ≥50 years diagnosed with EIBC (stage I–IIIa) in England and Wales between January 2014 and December 2018 who had a mastectomy within 12 months of diagnosis. A multilevel mixed-effects logistic regression model was used to calculate risk-adjusted rates of PMRT for geographical regions and National Health Service acute care organisations. The study examined the variation in these rates within subgroups of women with different risks of recurrence (low: T1-2N0; intermediate: T3N0/T1-2N1; high: T1-2N2/T3N1-2) and investigated whether the variation was linked to patient case-mix within regions and organisations. ResultsAmong 26 228 women, use of PMRT increased with greater recurrence risk (low: 15.0%; intermediate: 59.4%; high: 85.1%). In all risk groups, use of PMRT was more common among women who had received chemotherapy and decreased among women aged ≥80 years. There was weak or no evidence of an association between use of PMRT and comorbidity or frailty, for each risk group. In women with an intermediate risk, unadjusted rates of PMRT varied substantially between geographical regions (range 40.3–77.3%), but varied less for the high-risk (range 77.1–91.6%) and low-risk groups (range 4.1–32.9%). Adjusting for patient case-mix reduced the variation in regional and organisational PMRT rates to a small degree. ConclusionsRates of PMRT are consistently high across England and Wales among women with high-risk EIBC, but variation exists across regions and organisations for women with intermediate-risk EIBC. Effort is required to reduce unwarranted variation in practice for intermediate-risk EIBC.

Abstract PD6-10: PD6-10 The impact of post mastectomy radiation therapy on clinical outcomes of male breast cancer: A meta-analysis of comparative studies

Abstract Background/Rationale: Male breast cancer accounts for less than 1 percent of all cancer diagnoses in men. Because it is rare, it does not lend itself to large, randomized trials. In general, the approach to the treatment of early, non-metastatic male breast cancer has largely been extrapolated from female breast cancer trials. Specifically, the data on early-stage post mastectomy radiation therapy (PMRT) is limited, and its benefits remain unclear. Objectives: We conducted this meta-analysis to determine the impact of PMRT on clinical outcomes of men with breast cancer. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of invasive non-metastatic male breast cancer (MBC), comparative studies of PMRT versus none, and studies that reported the incidence of local and distant recurrences as well as survival data in the compared arms. A meta-analysis using the Mantel-Haenszel method for calculating the weighted pooled relative risk (RR) under the fixed effects model. Subsequently, the heterogeneity statistic gets incorporated to calculate the summary RR under the random effects model. Results: Ten retrospective comparative studies with 3912 patients were included and analyzed. Eight studies reported survival data. Six and three studies reported local and distant recurrence incidence, respectively. PMRT did not have an impact on overall survival or distant recurrences. However, PMRT significantly lowered the RR of locoregional recurrences (RR=0.53, 95%CI 0.31-0.92). In addition, when survival was analyzed by TNM stage and N status, PMRT was found to have a significant reduction in RR of death in stage III (RR=0.85, 95%CI 0.75-0.97), N1 (RR=0.77, 95%CI 0.61-0.98), and N2 (RR=0.61, 95%CI 0.49-0.78) disease. Conclusions: This is the first meta-analysis to show that PMRT is associated with a lower relative risk of death in stage III MBC as well as N1 and N2 disease. It also demonstrates a significant reduction in RR of locoregional recurrences. In the absence of randomized clinical trials, it represents the most compelling data supporting the use of PMRT in this MBC patient population. Citation Format: Philip A. Haddad, Usman Zaheer. PD6-10 The impact of post mastectomy radiation therapy on clinical outcomes of male breast cancer: A meta-analysis of comparative studies [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD6-10.

Patterns and Longitudinal Changes in the Practice of Breast Cancer Radiotherapy in Korea: Korean Radiation Oncology Group 22-01.

We aimed to analyze contemporary practice patterns in breast cancer radiotherapy (RT) and assess longitudinal changes over five years in Korea. In 2022, a nationwide survey was conducted among board-certified radiation oncologists. The survey consisted of 44 questions related to six domains: hypofractionated (HypoFx) whole breast RT, accelerated partial breast RT (APBI), regional nodal irradiation (RNI), RT for ductal carcinoma in situ (DCIS), postmastectomy RT (PMRT), and tumor bed boost. Seventy radiation oncologists from 61 (out of 101; 60%) institutions participated in the survey. HypoFx RT was used by 62 respondents (89%), a significant increase from 36% in 2017. HypoFx RT is commonly administered at 40-42.5 Gy in 15-16 fractions. APBI was used by 12 respondents (17%), an increase from 5% in 2017. The use of RNI did not change significantly: ≥ pN2 (6%), ≥ pN1 (33%), and ≥ pN1 with pathological risk factors (61%). However, indications for internal mammary lymph node (IMN) irradiation have expanded. In particular, the rates of routine treatment of IMN (11% from 6% in 2017) and treatment in cases of ≥ pN2 (27% from 14% in 2017) have doubled; however, the rate of treatment for only IMN involvement, identified on imaging, has decreased from 47% in 2017 to 31%. For DCIS, the use of HypoFx RT increased from 25% in 2017 to 75%, and the rate of RT omissions after breast-conserving surgery (BCS) decreased from 48% in 2017 to 38%. The use of HypoFx RT for PMRT increased from 8% in 2017 to 36%. The adoption of HypoFx RT after BCS for invasive breast cancer and DCIS has increased significantly, whereas the use of HypoFx PMRT has increased moderately since 2017. However, further studies are required to determine the optimal use of RNI.

Comparing Radiotherapy (RT) Late Toxicities to the Reconstructed DIEP Flap in Breast Cancer Patients Treated with Neoadjuvant RT (NART) vs. Post-Mastectomy RT (PMRT)

<h3>Purpose/Objective(s)</h3> The use of PMRT in patients undergoing immediate Deep Inferior Epigastric Perforator (DIEP) flap reconstructions is well known to cause significant long-term toxicity such as flap contracture, fat necrosis and cosmetic detriment. This can lead to significant long-term pain and impact on quality of life (QOL) (Yun et al, 2018). On the other hand, NART prior to the DIEP reconstruction performed in our institution has been shown to have no detriment in safety and local control but the long-term impact on the DIEP reconstruction remains unclear (Chidley et al, 2021). The aim of this retrospective study is to compare the long-term consequences of NART followed by DIEP versus immediate DIEP with PMRT on the reconstruction. <h3>Materials/Methods</h3> Retrospective comparison of long-term toxicities was done on the patient cohort who underwent NART followed by DIEP reconstruction (from 03/2013 to 09/2019) and patients who had immediate DIEP reconstruction followed by RT (from 01/2013 to 05/2021). Clinical examination was performed to assess the presence of fat necrosis (graded using the Wagner classification et al. 2013) and flap contracture. Breast cosmesis was graded using the Kroll classification (Kroll et al, 1994). Statistical analysis was performed to identify the rate of cosmesis problem, fat necrosis and flap contracture between these two patient's cohorts. <h3>Results</h3> Total of 155 patients who underwent NART and 31 patients who went through PMRT were analyzed. The median age of each cohort is 48 and 49 respectively for NART vs PMRT (p=0.26). Majority of patients in the NART and PMRT cohort received 50.4Gy/28# (78.6% [121] vs 74.2% [23]). Median follow up for NART and PMRT group was 32.5 months and 28.8 months respectively. No difference in local control was reported (98.1% NART vs 100% PMRT). Patients who had NART reported a higher satisfaction rating with their cosmesis. This was reported as ‘excellent to good' in 96.1% for NART compared to 80.1% for PMRT p<0.001. In addition, the risk of developing a flap contracture was significantly increased in patients who had PMRT (1.9% NART vs 41.9% PMRT; p<0.001). This was described as minimal in 29% and moderate in 12.9%. The risk of developing fat necrosis rate was also significantly increased in patients who had PMRT (12.9% NART vs 19.4% PMRT; p<0.001). While all fat necrosis in the NART cohort was grade 2, 50% of patients in the PMRT cohort had pain as well (grade 4). <h3>Conclusion</h3> Our retrospective analysis suggests that PMRT following immediate DIEP has significantly higher risk of late toxicities compared to NART followed by DIEP reconstruction. Whether this translates to a meaningful impact on QOL can only be determined by a randomized study.

21 Gene Recurrence Score to Select for Patients with T3N0 ER+HER2- Breast Cancer Likely to Benefit with Postmastectomy Radiation

<h3>Purpose/Objective(s)</h3> Postmastectomy radiation therapy (PMRT) is an option for patients with breast cancer who have T3N0 disease treated with mastectomy. Whether there is a benefit to PMRT in this subgroup of patients is a matter of debate. The 21 gene recurrence score (RS) can be used to select for patients likely to benefit from chemotherapy. Whether the use of the RS to select for patients likely to benefit from PMRT is currently not known. The purpose of the present study is to determine if the RS can select for patients with T3N0 ER+HER2- breast cancer likely to benefit from PMRT. The hypothesis is that patients with a low RS may not benefit from PMRT. <h3>Materials/Methods</h3> This study was conducted using patients from the National Cancer Data Base (NCDB). Patients included in this study were women diagnosed with ER+HER2- breast cancer with pT3N0 disease who were treated with mastectomy. The use of neoadjuvant chemotherapy was not allowed. Overall survival was compared between all patients using the Kaplan- Meier analysis and after stratifying patients by RS. Multivariable logistic regression ascertained factors associated with PMRT use. Cox proportional hazards modeling determined variables associated with OS. <h3>Results</h3> A total of 1,807 patients met the selection criteria, of whom 1,031 (57.1%) received PMRT, and 763 (42.2%) did not receive PMRT. Among all patients, use of PMRT was associated with improved OS (5-year OS 93.9% vs 89.5%, p=0.0079). After stratifying patients by RS, no OS difference was observed with the use of PMRT amongst patients with a low RS (5-year OS 95.0% vs 92.2%, p = 0.0941), whereas amongst patients with an intermediate/ high RS, improvement with the use of PMRT was observed (5-year OS 93.4% vs 88.5%, p = 0.0375). Factors predictive of PMRT use include use of chemotherapy and receipt of treatment at a nonacademic facility. On multivariate analysis, factors predictive of worse OS include increasing age, Charlson Deyo Comorbidity score ≥ 2, and omission of PMRT. <h3>Conclusion</h3> PMRT may have limited benefit in patients with ER+HER2- T3N0 breast cancer with a low RS. However, PMRT was associated with an OS benefit in these patients who had a high RS. Further research is required to confirm these findings and to determine the ability of the RS to select for patients most likely to benefit from PMRT.

Increasing Utilization of Regional Nodal Irradiation for Patients with Low-Risk Node-Positive Breast Cancer

<h3>Purpose/Objective(s)</h3> For patients with biologically low-risk, N1 breast cancer, the benefit of regional nodal irradiation (RNI) and post-mastectomy radiotherapy (PMRT) is unclear and is the subject of ongoing clinical trials. Population-level data of rates of RNI receipt is lacking in this cohort, and may be increasing despite its uncertain benefit. The purpose of this study was to determine if there was increasing use of RNI and PMRT for low-risk, N1 breast cancer. <h3>Materials/Methods</h3> This was a population-based study of all patients diagnosed between 2005 to 2014 in the [state/province] of [blinded], who underwent breast conserving surgery (BCS) or mastectomy for breast cancer. We based our definition of low-risk on the original inclusion criteria of MA.39/TAILOR RT trial, which is a non-inferiority clinical trial examining whether the omission of RNI is non-inferior. We included: pT1-2 pN1 (macroscopically node-positive) breast cancer. To define a biologically low-risk population, we included patients with a Luminal A subtype. This was approximated by: ER Allred 6-8/8, PR Allred 6-8/8, HER2-negative, and Grade 1-2. Patients who underwent a BCS and mastectomy were analyzed separately. The primary outcome was RNI receipt for patients who had a BCS, and PMRT receipt for those who had a mastectomy. We performed a multivariate, logistic regression to see whether year of diagnosis predicted for receipt of radiation. Other variables included in the multivariate model were defined a priori, based on factors known to influence RNI and PMRT receipt in the literature. <h3>Results</h3> There were 637 women who had BCS and 532 who had mastectomy in this cohort. For patients who had BCS, the rates of RNI receipt by years were: 2005-2008 68%, 2009-2011 79%, 2012-2014 89%. For patients who had a mastectomy, the rates of PMRT receipt by years were: 2005-2008 67%, 2009-2011 68%, 2012-2014 80%. During this time period, decreasing rates of ALND were observed: 2005-2008: 92%, 2009-2011 74%, 2012-2014 42%. On multivariate analysis of patients who had a BCS, RNI receipt was associated with number of involved macroscopic nodes (p=0.002) and date of diagnosis (p<0.001), but not age (p=0.2), presence of LVI (p=0.2), ALND (p=0.08), or chemotherapy receipt (p=0.9). For patients who had a mastectomy, PMRT receipt on multivariate analysis was associated with number of involved macroscopic nodes (p=0.02) and chemotherapy receipt (p=0.004), but not age (p=0.09), LVI (p=0.3), or diagnosis date (p=0.1). <h3>Conclusion</h3> There was an increased rate of RNI receipt, and a trend for increased receipt of PMRT for patients with low-risk, node-positive breast cancer between 2005 to 2014. This population-level data shows the large proportion of women who may be spared RNI if the MA.39 non-inferiority trial determines that omission of RNI is safe.

Benefits of post-mastectomy radiation for T4N0M0 breast cancer patients: A SEER Database study

Purpose: To evaluate the impact of post-mastectomy radiation therapy (PMRT) in breast cancer patients with stage T4N0M0.Method: Patients diagnosed with breast cancer of T4N0M0 from Jan 2010 to Dec 2015 were extracted from SEER database. Multivariable logistic regression was used to analyze the factors associated with PMRT. Univariate and multivariate COX regression were used to analyze factors that might be associated with breast cancer specific survival (BCSS) and overall survival (OS) of patients. Kaplan–Meier analysis was performed to evaluate BCSS and OS in different subtypes of patients.Result: Multivariable logistic regression showed that patients ≥ 71 years were less intend to have PMRT. Multivariate Cox analysis showed that married statue, HR+/Her- and HR+/Her+ subtypes, were independent predictors of improved BCSS and OS, and use of PMRT could improve BCSS and OS . PMRT was beneficial for OS in all subtypes breast cancer patients, but BCSS benefit was observed only in TNBC patients.Conclusion: The use of PMRT improves OS in all T4N0M0 patients, but in terms of BCSS, it only beneficial for TNBC patients.

Patterns of postmastectomy radiation therapy in clinically node-positive breast cancerpatients with pathologically negative lymph nodes after neoadjuvant chemotherapy.

To analyze postmastectomy radiation therapy (PMRT) utilization and its association with overall survival (OS) in patients presenting with node-positive breast cancer who are pathologically node-negative (ypN0) after neoadjuvant chemotherapy (NAC). Using the National Cancer Data Base (NCDB), we identified patients diagnosed between 2004 and 2013 with clinical T1-4 node-positive nonmetastatic breast cancer who received NAC and underwent mastectomy with pathologically negative lymph node sampling. Multivariable regression models identified factors associated with PMRT use. The Cox proportional hazards model was used to evaluate predictors of mortality. The study included 8766 clinically node-positive patients who met the study criteria. PMRT was delivered to 61.5% of patients. Overall PMRT utilization rate increased over the study period from 54.4% in 2004 to 65.2% in 2011. Predictors of PMRT use included larger tumor size, increasing clinical N stage, higher grade disease, receipt of hormone therapy, and a greater number of lymph nodes examined. The unadjusted 5-year OS was 84.1% in the PMRT group and 83.8% in the non-PMRT group (p = NS). PMRT was not significantly associated with survival on multivariable analysis (hazard ratio [HR] 0.87; 95% confidence interval [CI] 0.73-1.03). The delivery of PMRT has increased over time in women presenting with clinically node-positive breast cancer who convert to ypN0 after NAC. While we identified multiple independent socioeconomic and clinical predictors of both PMRT utilization and survival, PMRT itself was not significantly associated with survival.

Postmastectomy Radiation Therapy Following Pathologic Complete Nodal Response to Neoadjuvant Chemotherapy

<h3>Purpose/Objective(s)</h3> Postmastectomy radiation therapy (PMRT) is recommended for patients with breast cancer who have positive nodal disease. Whether there is a benefit to PMRT in patients who have cN+ disease at diagnosis, but a pathologic complete response following neoadjuvant chemotherapy (NAC) in the lymph nodes (pCRn) is unknown. The purpose of the present study is to determine if there is a benefit to PMRT in patients who have a pCRn following neoadjuvant chemotherapy, and which subsets of patients may derive the benefit from PMRT following a pCRn. <h3>Materials/Methods</h3> This study was conducted using patients from the National Cancer Data Base (NCDB). Patients included in this study were women diagnosed with breast cancer with cT1-4N1-3 disease who had invasive ductal carcinoma histology and received treatment with NAC and then mastectomy. Overall survival (OS) was compared between all patients using the Kaplan- Meier analysis. To further determine if subsets of patients may derive a greater benefit from PMRT, OS was compared after stratifying patients for clinical T stage, clinical N stage, pathologic T stage, and molecular subtype. Multivariable logistic regression ascertained factors associated with PMRT use. Cox proportional hazards modeling determined variables associated with OS. <h3>Results</h3> A total of 14,960 patients met the selection criteria, of whom 10,092 (67.5%) received PMRT, and 4598 (30.7%) did not. Amongst all patients, there was no difference in OS with the use of PMRT (10-year OS 76.3% vs 78.6%, <i>P</i> = 0.4147). Improvement with the use of PMRT was observed amongst patients with cN3 (10-year OS 73.1% vs 51.7%, <i>P</i> < 0.001), cT3 (10-year OS 77.0% vs 72.2%, <i>P</i> = 0.0154) or cT4 (10-year OS 69.6% vs 59.1%, <i>P</i> = 0.0001) disease, ypT2 (10-year OS 72.9% vs 65.0%, <i>P</i> = 0.0053) or ypT3 disease (10-year OS 62.3% vs 45.3%, <i>P</i> = 0.0466), as well as patients with ER+HER2+ disease (10-year OS 85.4% vs 56.5%, <i>P</i> = 0.0225). Factors predictive of PMRT use include younger age, Private health insurance, higher socioeconomic status, cT2/3/4 stage, and cN2/3 stage. On multivariate analysis, factors predictive of worse OS include increasing age, Charlson Deyo Comorbidity score ≥ 2, cT3 or cT4 disease, cN2 or cN3 disease, ypT1-4 disease, progression of the primary tumor after neoadjuvant chemotherapy, or ER-HER2- disease. <h3>Conclusion</h3> The extent of nodal disease and primary tumor size both at diagnosis and following NAC may be able to select for patients with pCRn most likely to benefit from PMRT. Further research is required to confirm these findings and to select the patients most likely to benefit from PMRT following NAC and mastectomy.

Isolated Tumor Cells and Micrometastatic Nodal Disease in Breast Cancer Patients After Neoadjuvant Chemotherapy: Is Post Mastectomy Radiation Therapy Indicated?

<h3>Purpose/Objective(s)</h3> The prognostic and treatment implications of isolated tumor cells (ypN0i+) and micrometastatic (ypN1mi) nodal disease after neoadjuvant chemotherapy (NACT) is not well-studied. These patients are excluded from the ongoing NSABP B-51 trial which only includes patients with macroscopic nodal disease after NACT. We evaluate the long-term outcomes and the role of post-mastectomy radiation therapy (PMRT) in breast cancer patients with ypN0i+ and ypN1mi disease after NACT and mastectomy (MX). <h3>Materials/Methods</h3> Using the National Cancer Database (NCDB), we identified patients (≥ 18 year old) with breast cancer who were treated with NACT and MX diagnosed between 2004 and 2016. Patients with cT4 or metastatic disease were excluded. Chi-square testing was used to evaluate clinicopathological parameters of those treated with and without PMRT. Kaplan-Meier analysis was used to evaluate the effect of PMRT on overall survival (OS). Univariate and multivariate Cox proportional hazard models with and without inverse probability treatment weighting (IPTW) were used to identify prognostic factors associated with OS. <h3>Results</h3> Our final cohort consisted of 3,253 patients (34.0% ypN0i+, 66.0% ypN1mi) with a median age at diagnosis of 49 years (29 – 74 years). PMRT was utilized in 60.4% of the entire cohort, 51.8% of ypN0i+ patients and in 64.9% of ypN1mi patients. There was an increase in use of PMRT throughout the study period (56.2% in 2004-2011 vs. 61.9% in 2012-2016). With a median follow up of 36.8 months, the 5-year OS was 84.3% and 79.9% for ypN0i+ and ypN1mi patients, respectively (HR 1.23 [0.97-1.55], <i>P</i> = 0.092). Without accounting for covariates, there was no significant effect of PMRT on OS in ypN0i+ patients, ypN1mi patients, or in the entire cohort. In IPTW-MVA, PMRT had no significant effect on OS (HR 0.93 [0.74-1.18], <i>P</i> = 0.565]. Factors that were significant for worse OS on IPTW-MVA were higher comorbidity score, higher grade, hormone-receptor negative subtype, higher ypT stage, presence of lymphovascular invasion, Asian/Pacific Islander race, and more recent year of diagnosis. HER-2 positive subtype, receipt of hormone therapy, and private insurance were associated with improved OS. <h3>Conclusion</h3> Patients with ypN1mi disease had a trend towards worse OS in comparison to patients with ypN0i+ disease. The majority of patients with ypN0i+ and ypN1mi are receiving PMRT with higher rates of PMRT in ypN1mi vs. ypN0i+. PMRT rates are increasing with time. There is no association of PMRT with improved OS. Prospective randomized controlled data is needed to further evaluate the role of PMRT in these patients who were excluded from the ongoing NSABP B-51.

Outcomes of Stage I and II Breast Cancer with Nodal Micrometastases Treated with Mastectomy without Axillary Therapy.

Studies that report equivalent oncologic outcomes of sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) for T1-2N1mi breast cancers are heavily weighted with patients who received breast-conserving surgery (BCS). The impact of omitting ALND in N1mi patients treated with mastectomy is not well studied. It is also unknown if these patients would benefit from post-mastectomy radiotherapy (PMRT). This study reports the outcomes of patients with T1-2N1mi breast cancer treated by mastectomy without axillary therapy. Patients who had T1-2N1mi breast cancer and underwent mastectomy from January 1998 to December 2018 were identified from our multi-institutional prospective database. Axillary recurrence rate (ARR), disease-free survival (DFS), and overall survival (OS) are reported. 260 patients with pT1-2N1mi breast cancer who had mastectomy were identified. They had either SLNB (35.4%) or ALND (64.6%). Majority of these patients received adjuvant systemic therapy (93.8%). 77 (29.6%) patients received radiotherapy, 31 after SLNB and 46 after ALND. At median follow-up of 61months, ARR was 1.1% (n = 1) in the SLNB only group, vs. 0.6% (n = 1) in the ALND group (p = 0.752). DFS and OS were not significantly different between patients with SLNB alone versus ALND (p = 0.40 and p = 0.27, respectively). Among 92 patients who had SLNB only, no DFS or OS difference was observed with the use of PMRT. In T1-2N1mi patients with mastectomy and SLNB, axillary recurrences were rare. No statistically significant differences were noted between patients with SLNB, ALND, or PMRT. Our findings suggest that these patients may be safely treated without axillary therapy.

Is it beneficial for patients with pT1‐2N1M0 breast cancer to receive postmastectomy radiotherapy? An analysis based on RecurIndex assay

The benefit of postmastectomy radiotherapy (PMRT) for pT1-2N1M0 breast cancer patients currently remains controversial. This study was conducted to investigate whether pT1-2N1M0 breast cancer patients could benefit from PMRT based on RecurIndex assay. The clinical data of 213 pT1-2N1M0 breast cancer patients were retrospectively analyzed. Through RecurIndex assay, 81 cases were assessed as the low risk, and 132 as the high risk. Compared to low-risk patients, high-risk patients especially those not receiving PMRT had a significantly increased risk of recurrence and metastasis, and worse 7-year local-regional recurrence-free interval (LRFI), distance recurrence-free interval (DRFI) and recurrence-free survival (RFS) rates. PMRT-based subgroup analysis indicated no significant differences between the low-risk patients with and without PMRT in 7-year LRFI, DRFI, RFS and overall survival (OS) rates, but apparent differences were all shown between the high-risk patients with and without PMRT in 7-year LRFI, DRFI, RFS and OS rates. Overall, for pT1-2N1M0 breast cancer patients at low risk of recurrence and metastasis stratified by RecurIndex assay, there may be a phenomenon of no PMRT benefits, while for those at high risk, use of PMRT may produce survival benefits.

Mastectomy alone for pT1-2 pN0-1 breast cancer patients: when postmastectomy radiotherapy is indicated.

To assess outcome of breast cancer (BC) stages pT1-2 N0-1 after mastectomy alone and to identify prognostic factors calling for the need of postmastectomy radiotherapy. Patients who were not eligible for breast conserving surgery (BCS) were operated on with mastectomy between 1998 and 2008. Locoregional (LRR), distant (DM) control and breast cancer specific survival (BCSS) were retrospectively evaluated. Cumulative incidence (CI) of events was estimated according to Kalbfleisch and Prentice while Gray's test tested difference. Kaplan-Meier method for survival and Cox proportional hazards model for univariable and multivariable analysis were used. A matched pair analysis between mastectomy alone and BCS plus whole breast irradiation (WBI), using the propensity score method, was performed. 1281 pT1-2 N0 and 1081 pT1-2 N1 were identified. Median follow-up was 8.2years (9.2years for survival). Overall, LRR rate was low for both N0 and N1 subgroups (10-year CI, 8.8% and 10.9%, respectively). Young age, lymphovascular invasion and Ki-67 ≥ 20% were proved to be statistically significant prognostic factors at multivariable analysis. The combination of ≥ 2 risk factors increased LRR rate to ≥ 15%. Risk factors combination weighed on LRR rate more than nodal status itself. DM rate doubled moving from negative to positive nodal status (10-year CI 10.5% versus 20.3%, respectively). BCSS remained high in both N0 and N1 subgroups (10-year CI 92.4% versus 84.5%, respectively). Remarkably, all the molecular subtypes except Luminal A significantly affected DM and BCSS both in the N0 and N1 subgroups. Nodes number significantly impacted on DM and BCSS but not on locoregional control. In the matched pair analysis, WBI decreased nodal recurrence rate and improved distant control, without affecting survival. Selected patients, namely those with at least two additional risk factors, presented high enough LRR risk to support the use of postmastectomy radiotherapy in both N0 and N1 subgroups. Moreover, the observation that radiotherapy may provide benefits that go beyond local control deserves to be further investigated.

Patterns of post-mastectomy radiation therapy in clinically node positive breast cancer patients with pathologically negative lymph nodes after neoadjuvant chemotherapy.

To analyze postmastectomy radiation therapy (PMRT) utilization and its association with overall survival (OS) in patients presenting with node positive breast cancer who are pathologically node negative (ypN0) after neoadjuvant chemotherapy (NAC). Using the National Cancer Data Base (NCDB), we identified patients diagnosed between 2004 and 2013 with clinical T1-4 node-positive non-metastatic breast cancer who received NAC and underwent mastectomy with pathologically negative lymph node sampling. Multivariable regression models identified factors associated with PMRT use. The Cox proportional hazards model was used to evaluate predictors of mortality. The study included 8,766 clinically node-positive patients who met the study criteria. PMRT was delivered to 61.5% of patients. Overall PMRT utilization rate increased over the study period from 54.4% in 2004 to 65.2% in 2011. Predictors of PMRT use included larger tumor size, increasing clinical N stage, higher grade disease, receipt of hormone therapy, and greater number of lymph nodes examined. Unadjusted 5-year OS was 84.1% in the PMRT group and 83.8% in the non-PMRT group (p=NS). PMRT was not significantly associated with survival on multivariable analysis (hazard ratio [HR] 0.87; 95% confidence interval [CI] 0.73-1.03). The delivery of PMRT has increased over time in women presenting with clinically node positive breast cancer who convert to ypN0 after NAC. While we identified multiple independent socioeconomic and clinical predictors of both PMRT utilization and survival, PMRT itself was not significantly associated with survival.

Analysis of Breast Cancer Patients with T1-2 Tumors and 1-3 Positive Lymph Nodes Treated with or without Postmastectomy Radiation Therapy

The use of postmastectomy radiation therapy (PMRT) has been recommended for patients with 4 or more positive lymph nodes, however, its role in patients with 1-3 positive lymph nodes remains unclear. The purpose of this study is to evaluate oncological outcomes for breast cancer patients with T1-2 tumors and 1-3 positive lymph nodes after undergoing PMRT. We performed a single-institution retrospective investigation that evaluated the association between PMRT and outcomes in breast cancer patients with T1-2 tumors and 1-3 positive lymph nodes, who underwent mastectomy from 2004 to 2015. Multivariable Cox proportional hazards regression was used to evaluate the association of PMRT with disease-free survival and overall survival. A total of 379 patients met inclusion criteria, of which 204 (54%) received PMRT while 175 (46%) did not receive PMRT following mastectomy and were followed over a median of 5.2 years (25th–75th percentile: 2.8–8.4 years). Recurrence was similar in patients receiving PMRT compared to those that did not: locoregional (0 vs 3, P = 0.061), distant (9 vs 3, P = 0.135) and any recurrence (11 vs 7, P = 0.525). After adjustment for potential confounding variables, PMRT was not associated with a statistically significant difference in disease-free survival (HR: 0.93; 95% CI: 0.48, 1.79) or overall survival (HR: 0.91; 95% CI: 0.45, 1.85). PMRT was not associated with improved oncological outcomes in patients with T1-2 breast cancer and 1-3 positive lymph nodes at our institution.

Identifying factors impacting the efficacy of postmastectomy radiotherapy in patients with early-stage breast cancer and one to two positive lymph nodes.

In women with T1-2 breast cancer and one to two positive axillary lymph nodes (LN) at low risk for recurrence, postmastectomy radiation therapy (PMRT) may provide insufficient benefit to justify its toxicity. This study evaluated the interaction of factors associated with overall survival (OS) after PMRT in these patients. The National Cancer Database was queried for women with T1-2 breast cancer undergoing mastectomy with one to two positive LN identified on lymphadenectomy. Patients were grouped according to number of positive LN and then stratified by PMRT use. Differences in OS were evaluated. Multivariable modeling demonstrated an interaction effect of age on the efficacy of PMRT. In patients more than or equal to 60 years old, PMRT was associated with improved survival when adjusting for age and tumor grade in patients with 1 to 2 positive LN (risk ratio = 0.62, 95% confidence interval = 0.40-0.93, P = .018). In patients less than 60 years old, tumor size and grade, but not PMRT, were associated with improved OS. For women with T1-2 breast cancer and one to two positive LN, PMRT's association with OS is influenced by age, tumor grade, and number of positive LN. PMRT appears to be associated with improvements in OS in older patients, but not younger patients, regardless of tumor size or nodal status.